Oral Medications For Acne

by

Michael H. Berkson, M.D.

In general, more moderate to severe acne tends to respond better to systemic treatment (oral medications) than to topical treatment alone. This is especially the case in the more inflammatory variants of acne.

The three main categories of systemic treatments for acne are antibiotics, hormonal treatments, which are used exclusively in women, and isotretinoin (formerly sold under the brand name Accutane). Each of these types of treatment has a different mechanism of action and a different indication depending upon the individual person and the type and severity of acne that they are experiencing.  Along with the advantages, all medications have disadvantages in the form of potential side effects that need to be taken into account when developing a treatment program.

Oral Antibiotics

Oral antibiotics have been a mainstay in the treatment of acne since the development of tetracycline in the 1960’s.  Despite the increasing issue of bacterial resistance, oral antibiotics still have a definite role in the treatment of moderate to severe acne.  It should be noted that most of the topics in the forthcoming discussion including concerns relating to bacterial resistance to oral antibiotics also apply to topical antibiotics.

Antibiotics have several mechanisms of action that are relevant to the treatment of acne.  Most important is their ability to kill the P.acnes bacteria and thus reduce the numbers of these bacteria in the pilosebaceous follicle, resulting in less inflammation. The tetracycline antibiotics also have a direct anti- inflammatory effect that is independent of the antimicrobial effect against P. acnes.

The most commonly used oral antibiotics are doxycycline ( Doryx, Monodox, Aticlate) and Minocycline, both of which are derived from the tetracycline molecule. Both are taken once or twice daily and can be very useful at reducing inflammatory acne.

Generally, Minocycline has a more potent effect against P. acnes and therefore tends to have a stronger clinical effect than doxycycline. Some of the reasons for this include the fact that minocycline gets into the follicle more efficiently as well as the fact that there is less bacterial resistance to minocycline than doxycycline.  The downside is that minocycline has more frequent side effects, the most common being an allergic reaction which usually takes the form of an uncomfortable rash. Dizziness and discoloration of the skin and teeth can also occur.  Severe, life threating reactions to minocyline, although rare, have been reported. Doxycycline sometimes causes gastrointestinal upset and increased sensitivity to the sun, but rarely allergic reactions.

Trimethoprim-sulfamethoxazole (Bactrim) is a sulfa derived antibiotic that is occasionally used for more severe acne that isn’t responding to minocycline. Like minocycline, it has a higher chance of allergic reactions compared to doxycycline.  All of the oral antibiotics have the potential to cause yeast infections in women.

Over many years, antibiotics, in general, have been slowly losing their effectiveness due to the emergence of resistant bacteria that result from genetic changes (mutations) within the organisms allowing them to adapt and survive in the presence of the antibiotics that were once lethal. The P. acnes bacteria is no exception and it has developed decreased sensitivity and strains that are resistant to clindamycin and erythromycin ( both used mainly topically) as well as doxycycline, and more recently, minocycline.  One of the consequences of bacterial resistance is that these drugs don’t work as well as they did previously and that they can lose their effectiveness in given individuals, over time, resulting in breakthrough acne and the need to switch to different treatments.

On global scale, the widespread use of antibiotics has selected for resistant strains of bacteria which are capable of causing severe infections that can even result in death.  An example is methcillin resistant Staph aureus (MRSA).

One of the methods that is used to try to maintain the effectiveness of antibiotics in the treatment of acne is to combine their use with benzoyl peroxide. Benzoyl peroxide (BPO) is a potent antimicrobial agent that is highly effective at killing P. acnes. To date, bacterial resistance to BPO has not been an issue. Several studies have shown that high concentrations of BPO can effectively reduce the appearance of less sensitive and resistant P. acnes when used concurrently with antibiotics.  For this reason, it is recommended that BPO, preferably in the form of a leave on gel cream or lotion, or high concentration wash, that is left on the skin for several minutes, be a part of the treatment regimen for anyone who is on antibiotics, either oral or topical, for the treatment of acne.

In summary, oral antibiotics still have an important place in the acne treatment armamentarium.  That said, judicious use is key. This means that they should only be used when necessary and only for as long as necessary and whenever possible, combined with benzoyl peroxide. Oral antibiotics are probably best used to calm moderate to severe inflammatory acne and serve as a bridge to other treatments such as isotretinoin (Accutane), hormonal treatment in women, or even aggressive topical treatment.

Hormonal Treatment

The androgen hormones  testosterone, dihydrotestosterone (DHT), and DHEAS are key factors in the development of acne.  The action of androgens on the sebaceous gland promotes the secretion of sebum into the sebaceous follicle which in turn promotes inflammation, comedogenesis, and the proliferation of P. acnes, all of which play a pivotal role in acne.  There are two primary types of treatment that have an effect on androgens and are thus beneficial in the treatment of acne in women. They are combination oral contraceptives and spironolactone.

Oral Contraceptives ( Birth Control Pills)

The combination birth control pill can be a moderately effective treatment for some women with acne, either alone, or even better, along with with other treatments.  It works by preventing the release of ovarian estrogen and progesterone and also inhibits the production, processing and action of ovarian and adrenal derived androgens, thus resulting in less sebum production by the sebaceous gland. Most forms of the combination birth control pill can be helpful in women with acne, however those containing less androgenic progestins such as drospirenone- Yasmin, Zarah, and Beyaz- probably have an advantage.

Although generally safe, the birth control pill should not be used in smokers and people with certain types of migraine headaches, because of the increased risk of blood clots, heart attack, and stroke.

Spironolactone (SPL)

Spironolactone ( SPL) is being used increasingly for the treatment of acne in women because of it’s androgen blocking and sebum suppressing properties.  It can be used at the same time as other topical and oral medications including the birth control pill. The drug has been around for many decades and is classified as a potassium sparing diuretic.   It is officially used for hypertension and heart failure and is used off label for acne.

Spironolactone blocks the androgen receptor on the sebaceous gland and also blocks the enzyme that converts testosterone to DHT  thus reducing sebum production, and through this mechanism, can be highly effective at controlling acne.  It is a good alternative to oral antibiotics and often works equally well and sometimes even better. Many who are not candidates for or choose not to go on isotretinoin ( Accutane) do quite well on SPL.

It’s side effect profile is quite favorable with more frequent urination (diuretic effect) being the most common issue. Menstrual irregularity, breast tenderness, and dizziness can also occur. Because of its effectiveness and safety SPL is a good long term option for women with acne. The only exception would be women who have kidney disease, take certain medications, or who are, or are trying to get pregnant.  Unfortunately, SPL is not a viable treatment option in men because it is not as effective and it can also have feminizing effects.

Isotretinoin ( Accutane)

Isotretinoin ( formerly sold under the brand name Accutane) remains the single most effective treatment for all types of acne.   Although officially indicated for severe nodular acne for which other treatments prove ineffective, it can also work extremely well for milder types of acne.

Isotretinoin is a synthetic derivative of vitamin A that works on most of the pathways that lead to acne. First and foremost, it is a potent suppressor of sebum production reducing oil output by the sebaceous glands to nearly zero. Isotretinoin also inhibits comedogenesis and has an anti-inflammatory effect.

An average course of isotretinoin lasts six months during which time most people’s acne clears completely. Many do not experience a significant recurrence of their acne after successful treatment with isotretinoin. And for those who’s acne does recur, an additional course of treatment is often a good option.

Although, highly effective, isotretinoin does have some common side effects the majority of which fall into the nuisance category.  Dry skin and chapped lips occur in everyone . Muscle and joint aches and a flare up of the acne at the beginning of treatment also happen with some regularity.   Elevated blood fats, especially triglycerides, occur in some and is screened for with a blood test before and during treatment.

The biggest concern with isotretinoin is that it is teratogenic, meaning that there is a high risk of major birth defects if a women were to become pregnant while on the drug.  For this reason, pregnancy tests are required for all women before treatment begins and monthly thereafter.  Ipledge, which is the isotretinoin risk management program, requires that women practice two approved forms of contraception for a month before, during, and for a month after completing treatment. Although isotretinoin is toxic to the developing fetus, it does not affect fertility in women or men.

There are  several controversies regarding isotretinoin and possible associations with mental health issues and inflammatory bowel disease.  There is a small subset of individuals who may be more prone to mood swings, increased anxiety, depression and aggressive behavior while on treatment.  There have been occasional reports of suicide in patients on isotretinoin.  None of the studies that have examined these issues have found a causal link between the drug and these behaviors.  In fact, the isotretinoin groups demonstrated less depression and better mental health outcomes than the control group of people with acne. With regard to inflammatory bowel disease ( ulcerative colitis and Crohn’s disease) there has never been a cause and effect association established between Isotretinoin and the onset of these conditions.

Despite some negatives, Isotretinoin remains a remarkable treatment that can change lives for the better in a big way.   It is unfortunately underutilized because too few practitioners understand it’s use and the subtleties and precautions that go along with its safe prescription.  The public is unnecessarily fearful as well, largely because of misinformation that gets promulgated online depicting “accutane horror stories.” There is no question that dermatologists are in the best position to help people succeed with isotretinoin and are the health providers of choice to help guide people through this treatment.

The next two articles are dedicated to  more in depth discussions of spironolactone and isotretinoin.  Both of these medications are assuming more prominent roles in the treatment of moderate and severe acne, in part because of the issue of antibiotic resistance.

References:

An Overview of Acne Therapy, Part 1: Topical therapy, Oral Antibiotics, Laser and Light Therapy, and Dietary Interventions.  Marson JW, Baldwin HE.  Dermatol Clin. 2019 Apr;37(2):183-193.

Guidelines of care for the management of acne vulgaris.  Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS, Bowe WP, Graber EM, Harper JC, Kang S, Keri JE, Leyden JJ, Reynolds RV, Silverberg NB, Stein Gold LF, Tollefson MM, Weiss JS, Dolan NC, Sagan AA, Stern M, Boyer KM, Bhushan R.  J Am Acad Dermatol. 2016 May;74(5):945-73.